Evidence map›Paper›PMID 23505158›Full record

ArticleStem cells (Dayton, Ohio)2013

Gene regulatory networks mediating canonical Wnt signal-directed control of pluripotency and differentiation in embryo stem cells.

Xiaoxiao Zhang, Kevin A Peterson, X Shirley Liu, Andrew P McMahon, Shinsuke Ohba

Open access · bronzeAbstract read
In one paragraph

Article in Stem cells (Dayton, Ohio), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
5.5field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

66 citing papers in PubMed, 106 citations in OpenAlex.

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6 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 2 countries.

Xiaoxiao ZhangDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, USA; Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, USA.
Kevin A Peterson
X Shirley Liu
Andrew P McMahon
Shinsuke Ohba
Harvard University · USDana-Farber Cancer Institute · US

Funding

The Roles of BMP Genes and Morphogenesis of the Appendicular and Dermal SkeletonsP01DK056246 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI DEMAY, MARIE, KRONENBERG, HENRY M. · 1999 to 2015
$19.3M
Cell Interactions in Development of the Mammalian KidneyR37DK054364 · NIDDK · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MCMAHON, ANDREW P. · 2008 to 2017
$7.0M
Computational Models for Mechanisms of Global Transcription RegulationR01HG004069 · NHGRI · DANA-FARBER CANCER INST · PI LIU, XIAOLE SHIRLEY · 2006 to 2013
$3.6M
NHGRI NIH HHS 2R01HG4069NHGRI NIH HHS R01 HG004069NIDDK NIH HHS DK056246NIDDK NIH HHS P01 DK056246NIDDK NIH HHS R37 DK054364
6 · The paper itself

Abstract

Canonical Wnt signaling supports the pluripotency of embryonic stem cells (ESCs) but also promotes differentiation of early mammalian cell lineages. To explain these paradoxical observations, we explored the gene regulatory networks at play. Canonical Wnt signaling is intertwined with the pluripotency network comprising Nanog, Oct4, and Sox2 in mouse ESCs. In defined media supporting the derivation and propagation of ESCs, Tcf3 and β-catenin interact with Oct4; Tcf3 binds to Sox motif within Oct-Sox composite motifs that are also bound by Oct4-Sox2 complexes. Furthermore, canonical Wnt signaling upregulates the activity of the Pou5f1 distal enhancer via the Sox motif in ESCs. When viewed in the context of published studies on Tcf3 and β-catenin mutants, our findings suggest Tcf3 counters pluripotency by competition with Sox2 at these sites, and Tcf3 inhibition is blocked by β-catenin entry into this complex. Wnt pathway stimulation also triggers β-catenin association at regulatory elements with classic Lef/Tcf motifs associated with differentiation programs. The failure to activate these targets in the presence of a mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) inhibitor essential for ESC culture suggests MEK/ERK signaling and canonical Wnt signaling combine to promote ESC differentiation.

Indexed as

Gene Regulatory NetworksAnimalsBase Sequencebeta CateninCell DifferentiationCell Growth ProcessesCell LineageEmbryonic Stem CellsMicePluripotent Stem CellsWnt Signaling Pathwaybeta CateninDifferentiationMouse embryonic stem cellsPluripotencyWntβ-catenin

Identifiers

PMID23505158
PMCPMC3830733
OpenAlexW1581784145

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.